DESCRIPTION (provided by candidate): The Mentored Clinical Scientist Research Career Development Award (K08) from NIDCR will provide the principal investigator who is an orthodontist with his background of periodontics and basic science training with the opportunity to receive additional scientific knowledge and research training in microRNA biology, epigenetics and drug development and protected time for his research activities. Recently emerging evidences show that microRNAs play a significant role in the development and remodeling of tissues through the regulation of large sets of extracellular matrix (ECM) genes. Orthodontic tooth movement is a complex biological event that involves the coordinated expression regulation of large sets of ECM genes, including a set of bone resorption effectors on the compression side and a set of matrix anabolic genes on the tension side. The principal investigator has demonstrated that microRNAs play important roles in tooth movement in a mouse model and different modes of forces induce different expression patterns of microRNA-21, 27 and29 as well as their target genes in cell cultures and a rat model. The hypothesis of this proposed research is that microRNA-21, 27 and 29 expression in periodontal tissues affects tooth movement by altering ECM gene expression levels, resulting in increased anabolic activity of ECM genes and new matrix deposition on the tension side in tandem with osteoclastogenesis and decreased bone mineral density on the compression side. The specific aims of this proposed research are 1) To determine and compare the effect of miR-21, 27 and 29 modulation on key periodontal cell types, periodontal ligament fibroblasts, osteoblasts, and osteoclasts, in 2- and 3-dimensional cell cultures and in response to mechanical loading; 2) To map the spatial and temporal expression of miR-21, 27 and 29 family expression during orthodontic tooth movement; 3) To determine the ability of miR-21, 27 and 29 mimics and inhibitors to affect the rate of tooth movement in a rat model. This career development award will involve didactic courses, laboratory rotations, a research project, and the guidance and expertise of world-class investigators. Under the mentorship of Drs. Salvador Nares and Thomas Diekwisch, and the experience and insights of a diverse Advisory Committee from the areas of microRNA biology, epigenetics, animal genetics and biopharmaceutics, the Career Development Award will ensure that the principal investigator can continue his professional development and achieve his goal of becoming an independent investigator. The training will be held mainly at the University of Illinois at Chicago (UIC) College of Dentistry with a number of laboratory rotation sessions at the Texas A&M University, the University of Pennsylvania and the University of Michigan at Ann Arbor for the principal investigator to gain his skills in the techniques and advice required in the research application. The ultimate goal of the proposed research is to improve orthodontic care by contributing to translational research and leading to the development of a novel microRNA-based approach as the principal investigator develops to be an independent orthodontist/ researcher.